Preparation and Evaluation of Chitosan-Based Controlled Drug Delivery Systems

Abstract

Controlled drug release enhances the safety, efficacy and reliability of the drug therapy. Regulation of the drug release rate results in the reduction in the frequency of drug administration and should encourage patients to comply with dosing instructions. These controlled release methods are more desirable patterns for drug administration, as the new and most powerful drugs continue to be developed. Many approaches were explored for controlled release of drug to the site of action, thus microspheres and hydrogels have received considered attention. In the present study, attempts have been made to prepare microspheres by emulsion cross-linking and hydrogels by physical cross-linking methods. The number of polymers suitable for controlled release of viable therapeutics is quite limited because of inherent toxicity or lack of certain properties such as biodegradability. In this thesis, chitosan is chosen as a base polymer, as it is non-toxic and biodegradable natural polymer. The interesting characteristics of chitosan make it ideal candidate for use in controlled drug release. Glutaraldehyde is used as cross-linking agent due to its commercial availability and low cost. Ampicillin loaded-chitosan microspheres were prepared by dropping the chitosan-drug solution in light liquid paraffin and span 80 emulsion, followed by adding the glutaraldehyde. The droplets instantaneously formed gelled spheres by emulsion cross-linking method. The effect of varying chitosan concentration on the preparation and properties of microspheres were studied. Microspheres were characterized by their percentage yield, particle size, surface morphology, drug encapsulation efficiency and in vitro drug release rate. Similarly hydrogels were prepared by preparing the chitosan-drug solution and then adding the glutaraldehyde, and stirring the solution for 15 minutes on the magnetic stirrer. Gelly type liquid forms by chemical cross-linking method. The effect of varying glutaraldehyde concentration and volume of glutaraldehyde was studied. They were characterized by their percentage yield, swelling ratio, surface morphology, drug encapsulation efficiency and in vitro drug release rate. In vitro drug release studies of microspheres and hydrogels both were done in buffer (pH 1.2) and subsequently in buffer (pH 6.8). The release of ampicillin from microspheres were affected by chitosan concentration i.e., increase in chitosan concentration decreases the release of drug. It was observed that highest efficiency and highest percentage release was achieved in the batch 1, having 1% (w/v) chitosan conc., 1% w/v drug concentration, 20 ml volume of chitosan-drug concentration and 2.5 hrs stirring time. In hydrogels, highest efficiency and highest percentage release was observed in batch 10, having 1% (w/v) chitosan concentration, 1% (w/v) drug concentration, 20 ml chitosan- drug solution, and with 15 minutes Stirring time. Chitosan microspheres crosslinked with the glutaraldehyde had good shape and good pH-responsive drug release properties. High drug incorporation in chitosan microspheres were obtained by emulsion cross-linking method, as by this method size of particles can be controlled by controlling the size of aqueous droplets. The chitosan hydrogels also show good pH-responsive properties. Both emulsion cross-linking and chemical cross-linking method can be carried out under very mild conditions using simple equipments. The control of various manufacturing parameters play a very important role in obtaining microspheres and hydrogels of high yield and high drug encapsulation, followed by high percentage release.